C-reactive protein (CRP) is an acute phase protein in humans that increases as much as several hundred-fold during acute pathological conditions. We have shown that natural killer (NK) cells have low levels of CRP on their surface and that NK function can be blocked with anti-CRP antibody. This implies that surface CRP (S-CRP) may be involved in the NK-mediated killing of tumor cell targets. We have tested 19 different monoclonal antibodies to CRP in the presence or absence of complement. Certain of these monoclonal antibodies eliminate NK function in the absence as well as the presence of complement. We have now used these monoclonal antibodies to show that CRP is on the effector cells that kill MOLT-4 targets, as well as on those effectors that kill K562, and that CRP does not seem to be involved in target cell recognition. We have developed a method for separating CRP+ and CRP- lymphocytes by rosetting with autologous human red blood cells that are coupled to the CRP ligand, C-polysaccharide. We have used this rosetting technique, as well as percol density gradient separation, to evaluate CRP+ and CRP- subpopulations. We have determined that the CRP+ subpopulation suppresses the NK activity of the CRP- subpopulation, and we are now evaluating the NK effector and suppressor activities of this CRP+ subpopulation of macrophage-depleted lymphocytes. (LB)